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Brachial plexopathy (BP) is a type of peripheral neuropathy which is caused by impaired function or damage of the brachial plexus, the nerves that control sensation and movement of the arm.

This neuropathy causes one to have decreased movement or sensation in the arm and shoulder, and can often cause severe pain and even paralysis of the arm.

BP is generally an uncommon adverse event in patients treated with radiation therapy to apical tumor sites. The rate of BP reported in various studies where patients receive 45-60 Gy with standard fractionation to the brachial plexus is approximately 1-6%.

Emami et. al. has observed the TD 5/5 for BP to be 60 Gy.

Although BP is not often reported for patients with breast or lung apical tumors treated with standard fractionation, it is of increasing concern in patients treated with hypofractionated regimens used in SBRT.

The purpose of this study was to report the frequency of BP in early stage NSCLC treated with SBRT and to evaluate dose predictors of toxicity for brachial plexus with hypofractionation.

Materials and Methods

Between 1998 and 2007, 253 patients (273 lesions) with Stage I or T3N0 NSCLC were treated with SBRT at Indiana University. Approximately 50% of these patients were treated on the RTOG 0236 SBRT protocol.

Of these patients, 36 patients (37 lesions) were identified as being apical tumor sites, defined as the center of the lesion superior to the aortic arch.

All patients were treated with 6-12 non-coplanar beams to the GTV volume with a 0.5 cm margin for CTV, and a 1 cm sup/inf margin for PTV. Patients were immobilized with a stereotactic body frame.

Toxicity data for ipsilateral shoulder/arm neuropathic pain, motor weakness, or sensory alteration for these 36 patients were reviewed for various time intervals following SBRT. BP was scored for apical lesions (AL) according to the CTCAE v. 3.0.

The ipsilateral brachial plexus was contoured retrospectively using the subclavicular/ axillary vessels as a surrogate to evaluate dose to that volume. It was determined that 26 Gy was the cutoff dose point for brachial plexus risk.

Results

36 patients of the 253 patients who received SBRT for early stage NSCLC were identified as having apical tumors. The median age of these patients was 73 years (range 57-81).

The median follow up was 13 months.

Median total dose was 57 Gy (30-72 Gy range) with a median treatment time of 8 days.

28/37 lesions were treated with 3 fractions and 9/37 lesions were treated with 4 fractions.

Most patients were treated to 80% isodose line.

At 2 years, the Kaplan Meier estimate for local control was 89% and OS was 64% for this subset.

Treatment of 7 of the 37 lesions caused brachial plexopathy.

Grade 2: 4 patients; Grade 3: 2 patients; Grade 4: 1 patient.

The one patient with severe toxicity suffered paralysis of her hand and wrist. This occurred at a median time of 7 months post treatment (range: 6-23 months).

Comparison of all apical lesions treated with SBRT (n=37) versus those with brachial plexopathy (n=7):

All apical lesions treated with SBRT (n=37)

Those with brachial plexopathy (n=7):

Median BP dose

26 Gy

30 Gy

Maximum BP BED

103 Gy3

123 Gy3

The 2 year Kaplan Meier risk of BP for patients receiving over 26 Gy to the brachial plexus was 46% vs. 8% in those who received <26 Gy. This was significantly different with a p=0.04. The same difference was seen when comparing patients with a maximum BP BED of >100 Gy3 versus those with <100 Gy3, with a significant p value as well.

The 1 patient with severe grade 4 BP had a dose of 72 Gy to the brachial plexus.

Author's Conclusions

SBRT offers excellent local control for patients with early stage apical inoperable lung cancers.

However, the authors concluded that there is a significant risk of brachial plexopathy for these patients, especially when the brachial plexus receives doses greater than 26 Gy. They emphasize the need to contour the brachial plexus when treating these patients and keep the dose to the BP to less than 26 Gy.

Tolerance doses for the brachial plexus by Emami et al. have been quoted as 60 Gy, which is equivalent to a BED=100 Gy3.

This study confirms that the max BED should be kept to <100 Gy3 for patients being treated with hypofractionated regimens as well to avoid risk of BP.

Clinical/Scientific Implications

Although SBRT is increasingly being used for treatment of patients with early stage inoperable lung cancer, this study highlights the importance of examining toxicity associated with hypofractionated regimens.

Brachial plexopathy is a debilitating condition for patients and can have a severe impact of one’s quality of life.

The brachial plexus is often not considered an organ at risk when treating patients with conventional radiation therapy for apical lung cancer, since doses of up to 60 Gy are well tolerated.

However, this study illustrates that with SBRT, the brachial plexus should be considered an organ at risk. In addition, studies such as these help us to understand the maximal tolerated dose of the brachial plexus when being treated with hypofractionation.

This study also provides important information for patients and clinicians when weighing the risks and benefits of SBRT.

The authors have shown a clear separation of BP in those who received greater than 26 Gy vs. less than 26 Gy to the brachial plexus. However, they did not use other cut off points besides 26 Gy. It would be interesting to see these results to determine if a lower dose is actually safer.

The study was well executed and designed, but the number of patients reviewed was small, and all BP contouring was done retrospectively which may lead to bias in these results. In addition, it is not clear if the methods of contouring the BP were standardized.

Longer follow up data is needed as well, since patients may develop BP even later than 2 years post RT, or symptoms may increase in severity with time.

In conclusion, it is important to determine threshold for dose to the brachial plexus when using SBRT to avoid BP in these patients with apical tumors. This study is a first attempt to do so, and further follow up may give us more information as to the maximal tolerated dose for these patients.

It is also critical to communicate this risk of BP with patients as well during informed consent as the risk is significant and may impact their ultimate treatment decision.

Dec 17, 2010 - Stereotactic body radiation therapy may be just as good as surgery for treating patients 75 years of age and older with early-stage non-small-cell lung cancer, according to research presented at the 2010 Chicago Multidisciplinary Symposium in Thoracic Oncology, held from Dec. 9 to 11.